👤 Shilpee Dutt

This study seeks a comprehensive exploration of genome-wide selective processes impacting morphometric traits across diverse cattle breeds, utilizing an array of statistical methods. Morphometric traits, encompassing both qualitative and quantitative variables, play a pivotal role in characterizing and selecting livestock breeds based on their external appearance, size, and physical attributes. While qualitative traits, such as color, horn structure, and coat type, contribute to adaptive features and breed identification, quantitative traits like body weight and conformation measurements bear a closer correlation with production characteristics. This study employs advanced genotyping technologies, including the Illumina BovineSNP50 Bead Chip and next-generation sequencing methods like Reduced Representation sequencing, to identify genomic signatures associated with these traits. We applied four intra-population methods to find evidence of selection, such as Tajima's D, CLR, iHS, and ROH. We found a total of 40 genes under the selection signature, that were associated with morphometric traits in five cattle breeds (Kankrej, Tharparkar, Nelore, Sahiwal, and Gir). Crucial genes such as ADIPDQ, DPP6, INSIG1, SLC35D2 in Kankrej, LPL, ATP6V1B2, CDC14B in Tharparkar, HPSE2, PLAG1 in Nelore, PCSK1, PRKD1 in Sahiwal, and GNAQ, HPCAL1 in Gir were identified in our study. This approach provides valuable insights into the genetic basis of variations in body weight and conformation traits, facilitating informed selection processes and offering a deeper understanding of the evolutionary and domestication processes in diverse cattle breeds. Show less

Glioblastoma (GBM) has poor median survival due to its resistance to chemoradiotherapy, which results in tumor recurrence. Recurrent GBMs currently lack effective treatments. DUSP6 is known to be pro-tumorigenic and is upregulated in GBM. We show that DUSP6 expression is significantly higher in recurrent GBM patient biopsies compared to expression levels in primary GBM biopsies. Importantly, although it has been reported to be a cytoplasmic protein, we found nuclear localization of DUSP6 in primary and recurrent patient samples and in parent and relapse populations of GBM cell lines generated from an in vitro radiation survival model. DUSP6 inhibition using BCI resulted in decreased proliferation and clonogenic survival of parent and relapse cells. Pharmacological or genetic inhibition of DUSP6 catalytic activity radiosensitized primary and, importantly, relapse GBM cells by inhibiting the recruitment of phosphorylated DNAPKcs (also known as PRKDC), subsequently downregulating the recruitment of phosphorylated histone H2AX (γH2AX) and 53BP1 (also known as TP53BP1). This resulted in decreased cell survival and prolonged growth arrest upon irradiation in vitro and significantly increased the progression-free survival in orthotopic mouse models of GBM. Our study highlights a non-canonical function of DUSP6, emphasizing the potential application of DUSP6 inhibitors in the treatment of recurrent GBM. Show less

Primary cultures of Müller cells have proven useful in cell biologic, developmental, and electrophysiological studies of Müller cells. However, the limited lifetime of the primary cultures and contamination from non-neural cells have restricted the utility of these cultures. The aim of this study was to obtain an immortalized cell line that exhibits characteristics of Müller cells. Primary Müller cell cultures were prepared from retinas of rats exposed to 2 weeks of constant light. Cells were immortalized by transfection with simian virus 40. Single clones were obtained by repeatedly passaging cells using cloning wells. Immunocytochemical and immunoblotting studies were carried out with glial fibrillary acidic protein (GFAP)-specific and cellular retinaldehyde-binding protein (CRALBP)-specific antibodies. Transient transfections with CRALBP-luciferase constructs were performed by electroporation. Oncogene transformation resulted in the establishment of a permanent cell line that could be readily propagated. Immunocytochemical and immunoblotting studies demonstrated that the Müller cell line, rMC-1, expressed both GFAP, a marker for reactive gliosis in Müller cells, and CRALBP, a marker for Müller cells in the adult retina. Transient transfection assays showed that promoter-proximal sequences of the CRALBP gene were able to stimulate reporter gene expression in rMC-1. Viral oncogene transformation has been successfully used to isolate a permanent cell line that expresses Müller cell phenotype. The rMC-1 cells continue to express both induced and basal markers found in primary Müller cell cultures as well as in the retina. The availability of rMC-1 should facilitate gene expression studies in Müller cells and improve our understanding of Müller cell-neuron interactions. Show less